Background: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood.
Objective: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients.
Methods: sVCAM-1 serum concentrations and whole blood mRNA expression were measured in blood samples from untreated RRMS-patients and from two independent groups of natalizumab-treated patients.
Results: sVCAM-1 serum concentrations and whole blood expression of HLX1 and IL1B mRNA were lower, whereas expression of EBI3 mRNA was higher in natalizumab-treated MS-patients. Five genes were differentially expressed in clinically unstable natalizumab-treated MS-patients in the discovery but not in the validation group.
Conclusion: Decreased serum concentrations of sVCAM-1 and altered whole blood mRNA expression levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HLX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status in natalizumab-treated MS.
Keywords: Disease modifying therapies; Immunology; Multiple Sclerosis; Natalizumab; Relapsing/remitting; SVCAM-1.
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